{"title":"Mutation-dependent treatment approaches for patients with complex multiple myeloma","authors":"F. Theodorakakou, M. Dimopoulos, E. Kastritis","doi":"10.1080/23808993.2021.1893605","DOIUrl":null,"url":null,"abstract":"ABSTRACT Introduction: Multiple myeloma is a complex hematologic malignancy that is considered incurable. The increasing comprehension of the genomic complexity has provided new insights into the therapeutic landscape of the disease. Next-generation sequencing studies have identified numerous driver gene mutations and alterations in signaling pathways, implicated in pathobiology and disease progression. Areas covered: Molecular tailored therapies against specific genetic alterations are under development in preclinical studies. These alterations include mutations in BRAF/KRAS/NRAS, FGFR3, overexpression of BCL2, and abberation in pathways such as MYC, JAK/STAT, NFκB, and PI3K/AKT/mTOR. Some of these novel anti-myeloma agents have entered clinical setting, as well. The question of whether these agents should be given as monotherapy or in combination with contemporary regimens is being addressed in ongoing trials. In the current review we present an up-to-date overview of targeted therapies MM. Expert opinion: Although fully personalized MM therapy is nowhere near, new technologies that allow rapid, detailed (and at a feasible cost) evaluation of the genetic content of myeloma on an individual basis may actually allow the development of therapies based on molecular profiling. These regimens may also have the potential to predict prognosis and achieve durable responses when established therapies are unable to overcome drug resistance.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.0000,"publicationDate":"2021-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1893605","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Precision Medicine and Drug Development","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/23808993.2021.1893605","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
ABSTRACT Introduction: Multiple myeloma is a complex hematologic malignancy that is considered incurable. The increasing comprehension of the genomic complexity has provided new insights into the therapeutic landscape of the disease. Next-generation sequencing studies have identified numerous driver gene mutations and alterations in signaling pathways, implicated in pathobiology and disease progression. Areas covered: Molecular tailored therapies against specific genetic alterations are under development in preclinical studies. These alterations include mutations in BRAF/KRAS/NRAS, FGFR3, overexpression of BCL2, and abberation in pathways such as MYC, JAK/STAT, NFκB, and PI3K/AKT/mTOR. Some of these novel anti-myeloma agents have entered clinical setting, as well. The question of whether these agents should be given as monotherapy or in combination with contemporary regimens is being addressed in ongoing trials. In the current review we present an up-to-date overview of targeted therapies MM. Expert opinion: Although fully personalized MM therapy is nowhere near, new technologies that allow rapid, detailed (and at a feasible cost) evaluation of the genetic content of myeloma on an individual basis may actually allow the development of therapies based on molecular profiling. These regimens may also have the potential to predict prognosis and achieve durable responses when established therapies are unable to overcome drug resistance.
期刊介绍:
Expert Review of Precision Medicine and Drug Development publishes primarily review articles covering the development and clinical application of medicine to be used in a personalized therapy setting; in addition, the journal also publishes original research and commentary-style articles. In an era where medicine is recognizing that a one-size-fits-all approach is not always appropriate, it has become necessary to identify patients responsive to treatments and treat patient populations using a tailored approach. Areas covered include: Development and application of drugs targeted to specific genotypes and populations, as well as advanced diagnostic technologies and significant biomarkers that aid in this. Clinical trials and case studies within personalized therapy and drug development. Screening, prediction and prevention of disease, prediction of adverse events, treatment monitoring, effects of metabolomics and microbiomics on treatment. Secondary population research, genome-wide association studies, disease–gene association studies, personal genome technologies. Ethical and cost–benefit issues, the impact to healthcare and business infrastructure, and regulatory issues.